Advertisement

Concurrent Identification of Novel EGFRSEPT14 Fusion and ETV6RET Fusion in Secretory Carcinoma of the Salivary Gland

  • Margaret BlackEmail author
  • Cheng Z. Liu
  • Maristela Onozato
  • Anthony John Iafrate
  • Farbod Darvishian
  • George Jour
  • Paolo Cotzia
Case Report

Abstract

Salivary gland secretory carcinoma, also termed mammary analogue secretory carcinoma (MASC), is a recently described salivary gland neoplasm with characteristic histomorphologic findings similar to those of secretory carcinoma of the breast and harboring recurrent ETV6NTRK3 fusions. Recent findings have expanded the molecular profile of salivary gland secretory carcinoma to include multiple novel ETV6 fusion partners, including RET, MET, and MAML3. Here, we report a case of cystic MASC with cribriform and papillary histology harboring two gene fusions, ETV6–RET and EGFR–SEPT14, identified by targeted RNA sequencing. The presence of the rearrangements was confirmed by FISH, RT-PCR, and Sanger sequencing. This is the first EGFR–SEPT14 fusion reported in secretory carcinoma as a single event or in association with an ETV6 rearrangement. This finding adds to the expanding molecular profile of this tumor entity, and may translate into novel treatment strategies.

Keywords

Secretory carcinoma Mammary analogue secretory carcinoma Salivary gland carcinoma ETV6 fusion EGFR–SEPT14 

Notes

Funding

None.

Compliance with Ethical Standards

Conflict of interest

The authors report no conflicts of interests.

References

  1. 1.
    Skalova A, Vanecek T, Sima R, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6–NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34:599–608.Google Scholar
  2. 2.
    Diallo R, Schaefer KL, Bankfalvi A, et al. Secretory carcinoma of the breast: a distinct variant of invasive ductal carcinoma assessed by comparative genomic hybridization and immunohistochemistry. Hum Pathol. 2003;34:1299–305.CrossRefGoogle Scholar
  3. 3.
    Schwartz LE, Begum S, Westra WH, Bishop JA. GATA3 immunohistochemical expression in salivary gland neoplasms. Head Neck Pathol. 2013;7:311–5.CrossRefGoogle Scholar
  4. 4.
    Laco J, Svajdler M Jr, Andrejs J, et al. Mammary analog secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/myoepithelial markers (calponin, CD10 and p63 protein). Pathol Res Pract. 2013;209:167–72.CrossRefGoogle Scholar
  5. 5.
    Tognon C, Knezevich SR, Huntsman D, et al. Expression of the ETV6–NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002;2:367–76.CrossRefGoogle Scholar
  6. 6.
    Ito Y, Ishibashi K, Masaki A, et al. Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion. Am J Surg Pathol. 2015;39:602–10.CrossRefGoogle Scholar
  7. 7.
    Skalova A, Vanecek T, Simpson RH, et al. Mammary analogue secretory carcinoma of salivary glands: molecular analysis of 25 ETV6 gene rearranged tumors with lack of detection of classical ETV6–NTRK3 fusion transcript by standard RT-PCR: report of 4 cases harboring ETV6-X gene fusion. Am J Surg Pathol. 2016;40:3–13.CrossRefGoogle Scholar
  8. 8.
    Skalova A, Vanecek T, Martinek P, et al. Molecular profiling of mammary analog secretory carcinoma revealed a subset of tumors harboring a novel ETV6–RET translocation: report of 10 cases. Am J Surg Pathol. 2018;42:234–46.CrossRefGoogle Scholar
  9. 9.
    Rooper LM, Karantanos T, Ning Y, Bishop JA, Gordon SW, Kang H. Salivary secretory carcinoma with a novel ETV6–MET fusion: expanding the molecular spectrum of a recently described entity. Am J Surg Pathol. 2018;42:1121–6.CrossRefGoogle Scholar
  10. 10.
    Guilmette J, Dias-Santagata D, Nose V, Lennerz JK, Sadow PM. Novel gene fusions in secretory carcinoma of the salivary glands: enlarging the ETV6 family. Hum Pathol. 2019;83:50–8.CrossRefGoogle Scholar
  11. 11.
    Drilon A, Li G, Dogan S, et al. What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6–NTRK3 identification in a mammary analogue secretory carcinoma (MASC). Ann Oncol. 2016;27:920–6.CrossRefGoogle Scholar
  12. 12.
    Sethi R, Kozin E, Remenschneider A, et al. Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland malignancy. Laryngoscope. 2014;124:188–95.CrossRefGoogle Scholar
  13. 13.
    Shigeta R, Orgun D, Mizuno H, Hayashi A. Mammary analogue secretory carcinoma arising in the parotid gland of child. Plast ReconstrSurg Glob Open. 2018;6:e2059.CrossRefGoogle Scholar
  14. 14.
    Zheng Z, Liebers M, Zhelyazkova B, et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20:1479–84.CrossRefGoogle Scholar
  15. 15.
    Knezevich SR, Garnett MJ, Pysher TJ, Beckwith JB, Grundy PE, Sorensen PH. ETV6–NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Can Res. 1998;58:5046–8.Google Scholar
  16. 16.
    Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61:387–94.CrossRefGoogle Scholar
  17. 17.
    Cipriani NA, Blair EA, Finkle J, et al. Salivary gland secretory carcinoma with high-grade transformation, CDKN2A/B Loss, distant metastasis, and lack of sustained response to crizotinib. Int J Surg Pathol. 2017;25:613–8.CrossRefGoogle Scholar
  18. 18.
    Luo W, Lindley SW, Lindley PH, Krempl GA, Seethala RR, Fung KM. Mammary analog secretory carcinoma of salivary gland with high-grade histology arising in hard palate, report of a case and review of literature. Int J Clin Exp Pathol. 2014;7:9008–22.Google Scholar
  19. 19.
    Skalova A, Vanecek T, Majewska H, et al. Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6–NTRK3 gene fusion and analysis of TP53, beta-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38:23–33.CrossRefGoogle Scholar
  20. 20.
    Khotskaya YB, Holla VR, Farago AF, Mills Shaw KR, Meric-Bernstam F, Hong DS. Targeting TRK family proteins in cancer. Pharmacol Ther. 2017;173:58–66.CrossRefGoogle Scholar
  21. 21.
    Frattini V, Trifonov V, Chan JM, et al. The integrated landscape of driver genomic alterations in glioblastoma. Nat Genet. 2013;45:1141–9.CrossRefGoogle Scholar
  22. 22.
    Williams L, Chiosea SI. Mammary analogue secretory carcinoma mimicking salivary adenoma. Head Neck Pathol. 2013;7:316–9.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathologyNew York University Langone HealthNew YorkUSA
  2. 2.Department of PathologyMassachusetts General HospitalBostonUSA

Personalised recommendations